The Claessen lab addresses fundamental questions related to multicellular growth and development in filamentous bacteria called streptomycetes. By making use of genetic, biochemical, cell-biological, and various next-generation sequencing technologies we use a multidisciplinary approach to understand and control the physiology of these bacteria. Our aim is to answer key questions related to cell functioning including cell morphogenesis, cell signaling, and protein transport and folding.
Tackling Streptomyces growth heterogeneity for improved productivity
The majority of clinically important antibiotics that are used to combat bacterial infections are derived from streptomycetes. In addition to antimicrobials, and also other medically relevant natural products including anticancer agents, these organisms produce numerous enzymes for medical and technical applications. Many of these enzymes are most efficiently produced by streptomycetes themselves (i.e. not by other cell factories), because they require host-specific machinery for their folding, modification and release into the medium. Growth of streptomycetes in fermenters is characterized by the formation of so-called pellets of interconnected filaments known as hyphae. The typical size heterogeneity of these pellets strongly reduces the desired specific productivity, which is one of the main reasons for the sub-optimal performance of streptomycetes in bioreactors. My lab tackles the heterogeneity in productivity by applying innovative cell-wall engineering approaches. This knowledge will be used to develop Streptomyces cell factories that are tailored for the production of (novel) enzymes and antimicrobials.
The role of functional amyloids in morphogenesis
Within the bacterial domain streptomycetes have an unusual life cycle. These microorganisms colonize dead and living organic material by means of hyphae that grow at their apices. The hyphae are part of an interconnected network, which is called a mycelium. At a certain moment, hyphae grow out of the substrate into the air. The aerial hyphae eventually septate to form chains of exospores that, after dispersal, give rise to new mycelia. Streptomycetes not only grow in moist substrates or in the air but they may also grow over and attach to hydrophobic surfaces such as the leaf of a plant or the skin of an animal. The Claessen lab is interested in the mechanisms enabling streptomycetes to leave the aqueous environment and to grow into the air or to attach to a hydrophobic solid. Two classes of proteins, called chaplins and rodlins, were identified that are involved in these processes. Strikingly, chaplins function by assembling into small amyloid-like fibrils at the hyphal surface. Amyloids are filamentous protein structures ±10 nm wide and 0.1–10 μm long that share a structural motif, the cross-β structure. These fibrils are usually associated with degenerative diseases in mammals (like Alzheimer’s). This work has demonstrated that amyloids can also be beneficial to some microbes enabling them to mechanically invade abiotic and biotic substrates.
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